Optional analyses of crossover trials having two treatments and a placebo


Abstract


The assumption of carryover effects is unavoidable due to the very nature of crossover designs. Even in case of crossover design with washout period, the hypothesis of no carryover effect should be tested and established. On the other hand, this assumption makes the analysis difficult and potentially biased or inefficient in case of two treatment two period crossover design. For a reasonable estimation, experimenters are advocated to employ a two period three treatment crossover designs, or a three period two treatment crossover design. In this article, we present optional analyses of a uniform three period three treatment crossover design, consisting of a placebo and two active treatments. We develop a test for detecting presence of carryover effects which directs experimenter for a proper analysis of his crossover trial. We present ANOVA for each of the three possible carryover models, that both, single, or none of the active treatments has carryover effect, and illustrate through an example.

DOI Code: 10.1285/i20705948v13n1p16

Keywords: Repeated measurement design; Carryover effects; Active treatment; Placebo treatment; Test of carryover effects; Analysis of variance

References


Afsarinejad, K. and Hedayat, A. (2002). Repeated measurements designs for a model with self and mixed carryover effects. Journal of Statistical Planning and Inference, 106:449 – 459.

Divecha, J. and Gondaliya, J. (2015). Estimation of treatment and carryover effects in optimal cross-over designs for clinical trials. Statistics in Biopharmaceutical Research, 7:95 – 105.

Ebbutt, A. (1984). Three-period crossover designs for two treatments. Biometrics, 40:219 – 224.

Grizzle, J. (1965). The two-period change-over design and its use in clinical trials. Biometrics, 6:467 – 480.

Hanford, K. (2005). In Lecture Notes on Mixed Models. Spring, United States.

Hedayat, A. and Stufken, J. (2003). Optimal and efficient crossover designs under different assumptions about the carryover effects. Journal of Biopharmaceutical Statistics, 13:519 – 528.

Hedayat, A. and Yang, M. (2004). Universal optimality for selected crossover designs. Journal of American Statistical Association, 99:461 – 466.

Jones, B. and Donev, A. (1996). Modelling and design of cross-over trials. Statistics in Medicine, 15:1435 – 1446.

Kempton, R., Ferris, S., and David, O. (2001). Optimal change-over designs when carryover effects are proportional to direct effects of treatments. Biometrika, 88:391 – 399.

Koch, G., Amara, I., Brown, B., Colton, T., and Gillings, D. (1989). A two-period crossover design for the comparison of two active treatments and placebo. Statistics in Medicine, 8:487 – 504.

Kunert, J. (1991). Crossover designs for two treatments and correlated errors. Biometrika, 78:315 – 324.

Laird, N., Skinner, J., and Kenward, M. (1992). An analysis of two-period crossover designs with carry-over effects. Statistics in Medicine, 11:1967 – 1979.

Lehmacher, W. (1991). Analysis of cross-over trials in the presence of residual effects. Statistics in Medicine, 10:891 – 899.

Lucas, H. (1957). Extra-period latin square changeover designs. Journal of Dairy Science, 4:225 – 239.

Martin, R. and Eccleston, J. (1998). Variance-balanced change over designs for dependent observations. Biometrika, 85:883 – 892.

Senn, S. (1992). Is the simple carryover model useful? Statistics in Medicine, 11:715 – 726.

Senn, S. and Lambrou, D. (1998). Robust and realistic approach to carry-over. Statistics in Medicine, 17:2849 – 2864.

Tsoy, A., Cheltzov, O., Zaseyeva, V., Shilinish, L., and Yashina, L. (1990). Preventive effect of formoterol aerosol in exercise-induced bronchoconstriction. European Respiratory Journal, 3:235s.

Yang, M. and Stufken, J. (2008). Optimal and efficient crossover designs for comparing test treatments to a control treatment under various models. Journal of Statistical Planning and Inference, 138:278 – 285.


Full Text: pdf


Creative Commons License
This work is licensed under a Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia License.